Low frequency and variability of FLT3 mutations in Korean patients with acute myeloid leukemia.
FLT3 mutations are common genetic changes, and are reported to have prognostic significance in acute myeloid leukemia (AML). The FLT3 internal tandem duplication (ITD) and the D835 activating mutation in the tyrosine kinase domain (TKD) were analyzed by polymerase chain reaction (PCR) in the genomic DNA of Korean patients with AML at diagnosis and during follow-up. There were 226 patients with AML enrolled between March 1996 and August 2005. The incidence of ITD and TKD at diagnosis was 13% (29/226) and 3% (6/226). When compared to Western and other Asian patients with AML, Korean patients had a lower frequency by about two-thirds of ITD and TKD. Among the non-M3 cases (N=203), the patients with an ITD had a significantly shorter event-free survival when compared with those without an ITD (p=0.0079). Among 54 relapsed patients, 9 patients had the FLT3 ITD at diagnosis. Six patients demonstrated a reappearance of the ITD and 3 patients remained negative at relapse. One patient, among 45 patients who relapsed, had a negative baseline ITD but acquired a de novo ITD at relapse. There were 101 samples from 93 patients in remission; they were all negative for an ITD. Among 34 patients who failed to achieve a remission, five patients had a persistent ITD and one patient had a de novo ITD. These results support the concept of resistance of FLT3 ITD leukemic clones to chemotherapy. Therefore, effective therapy with FLT3 targeting agents may improve the prognosis of non-M3 AML patients with the FLT3 mutation.
Bang
Soo-Mee
SM
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Ahn
Jeong Yeal
JY
Park
Jiyoon
J
Park
Se Hoon
SH
Park
Jinny
J
Cho
Eun Kyung
EK
Shin
Dong Bok
DB
Lee
Jae Hoon
JH
Yoo
Soo Jin
SJ
Jeon
In Sang
IS
Kim
Yeo-Kyeoung
YK
Kim
Hyeoung Joon
HJ
Kim
Hee-Nam
HN
Lee
Il-Kwon
IK
Kang
Hyoung Jin
HJ
Shin
Hee Young
HY
Ahn
Hyo Seop
HS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007723:Korea; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D051941:fms-Like Tyrosine Kinase 3